CN101502541A - Styrax plant and use of extract thereof - Google Patents
Styrax plant and use of extract thereof Download PDFInfo
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Abstract
The invention relates to a pharmaceutical use of styrax. The invention particularly relates to use of the styrax in the preparation of acyl coenzyme A: cholesterol acyltransferase (ACAT) inhibitor, and the styrax can be prepared into injections, oral tablets, capsules and a variety of preparations for being applicable to preventing and treating atherosclerosis, hyperlipidemia and other diseases. Furthermore, the styrax can be used as a preventive drug or a therapeutic agent for angina, myocardial infarction, cerebral infarction, Alzheimer's disease, acute coronary syndrome, PTCA or posterior coronary artery re-stenosis with stent and other diseases. The styrax can also be used as the therapeutic agent for regulating the functions of sebaceous glands and inhibiting excessive production of sebum, thereby being used for treating oily skin, acne, seborrhea, acne-like injuries caused by corticosteroids and other diseases.
Description
Technical field
The present invention relates to a kind of new pharmaceutical use of Chinese medicine extract, specifically, relate to a kind of Styrax plant and extract thereof and preparing acyl-CoA: the purposes in the chole-sterol acyltransferase inhibitor class medicine belongs to the field of Chinese medicines.
Background technology
Styracaceae (Styracaceae) has another name called Styracaceae, olive section, and about 11 belong to 180 kinds.China produces 9 and belongs to, and 50 kinds, 9 mutation, it is very wide to distribute.Styraax (Styrax Linn) has another name called snowball and belongs to, and about 130 kinds, China has 30 kinds approximately, 7 mutation, and main product is each provinces and regions on the south the Yangtze river basin.Styracaceae plant major part can be for viewing and admiring usefulness, the kind that has for material with or medicinal, its resin contains more balsamic acid, claims " Benzoinum ", the refreshing clearly circulation of qi promoting of having one's ideas straightened out arranged, invigorate blood circulation, the analgesic effect, be valuable medicinal pharmaceutically; This resin also can be used for making senior aromatic oil.The medical value aspect of fruit, the oil that extracts from the fruit of Styrax tonkinensis (being styrax tonkinensis Craib ex Hart) are exactly famous " white flower oil ", and hyoscine has sterilization, analgesic effect.Modern study shows, the main oil-containing of Styrax plant fruit, saccharide, lignin and new lignin (2-aryl benzofurans).According to bibliographical information, the fruit of Styrax plant, leaf, stem and tuber all contain 2-aryl benzofurans chemical constituent, wherein the content in fruit is the highest (Akgul YY, Anil H.Benzofurans and another constituent from seeds ofStyrax officinalis.Phytochemistry, 2003; 63:939-943; Takanashi M, Takizawa Y.New benzofurans related to egonol from immature seeds of Styrax obassia.Phytochemistry, 1988; 27:1224-1226; Anil H.Four benzofuran glycosides fromStyrax officinalis.Phytochemistry, 1980; 19:2784-2786; Min, Byung-Sun et al.Anti-complement activity of norlignans and terpenes from the stem bark of Styraxjaponica.Planta Medica, 2004; 70 (12): 1210-1215; Takanashi M, Takizawa Y, Mitsuhashi T.5-(3-Hydroxypropyl)-2-(3 ', 4 '-methylenedioxyphenyl) benzofuran:a new benzofuran from Styrax obassia Sieb.et Zucc.Chem.Lett., 1974; 869-871).There is research to report that its 2-aryl benzofuran constituents has certain antibiotic and anti-tumor activity (Pauletti PM, Ara ú jo AR, Marx Young MC, Giesbrecht AM and Bolzani VS.nor-Lignans from the leaves of Styrax ferrugineus (Styracaceae) with antibacterialand antifungal activity.Phytochemistry, 2000; 55 (6): 597-601; Tsai IL, Hsieh CF, Duh CY.Additional cytotoxic neolignans from Persea obovatifolia.Phytochemistry, 1998; 48:1371-1375); Patent CN1830435, CN1830976, CN1830980 etc. disclose the application of extractive of total benzofuran of benzoin plants in prevention or treatment premature ovarian failure, climacteric syndrome, osteoporosis and adolescence ovarian hypofunction, polycystic ovary syndrome, infertility and the disease that causes because of estrogen deficiency or relative deficiency.
Acyl-CoA: cholesterol acyltransferase (ACAT) is the enzyme that interior catalysis free cholesterol of cell and fatty acid generate cholesteryl ester, is one of key enzyme of cholesterol and esters metabolic balance thereof.Cholesteryl ester can produce the atheroma pathological changes large-area the accumulating of blood vessel, forms lipid-rich spot, and the destruction of lipid-rich spot can form thrombosis, produce the obstruction of coronary artery lumen, thereby causes diseases such as acute coronary syndrome, angina pectoris, myocardial infarction.The speckle that atheromatosis is deformed into forms at carotid artery and cerebral blood vessel then can cause cerebral infarction, so these diseases and atherosclerosis, hyperlipemia are closely related.The activity that suppresses this enzyme can be to all wielding influence in the physiological process such as cholesterol absorption, transhipment, distribution and metabolism, thus blood fat reducing, and can stop atherosclerotic early lesion.So the ACAT inhibitor can be used as preventive drug or the therapeutic agent that atherosclerosis, hyperlipemia, angina pectoris, myocardial infarction, cerebral infarction, Alzheimer, acute coronary syndrome, PTCA (percutaneous transluminal coronary angioplasty) or support are placed diseases such as back coronary restenosis.In addition, report ACAT inhibitor such as existing document US 6133326, CN1863521A can suppress the sebaceous gland sebum and generate, can be used as and regulate the sebaceous gland function, suppress the therapeutic agent that sebum excessively generates, be used for the treatment of the diseases such as acne sample infringement that oily skin, acne, seborrhea, corticosteroid cause.
Still do not have Styrax plant 2-aryl benzofuran extract so far and be used to prevent or treat relevant document record or the research report that atherosclerosis, hyperlipemia, angina pectoris, myocardial infarction, cerebral infarction, Alzheimer, acute coronary syndrome, PTCA or support are placed diseases such as back coronary restenosis, the excessive generation of sebum as the ACAT inhibitor.
Summary of the invention
Technical scheme of the present invention is the new purposes of Styrax plant.Another technical scheme of the present invention has provided a kind of be used for the treatment of or prevention of arterial is atherosis, the pharmaceutical composition of hyperlipemia.
The invention provides a kind of Styrax plant and extract thereof and preparing acyl-CoA: the purposes in the chole-sterol acyltransferase inhibitor class medicine.
Wherein, described Benzoinum derives from Styrax plant watt mountain Benzoinum Styrax perkinsiae, high post spring Benzoinum S.macranthus Perk., Chuxiong Benzoinum S.limprichtii Lingelsh et Borza, Styrax tonkinensis S.tonkinensis (Pierre) Craib et Hartw., Zhejiang Benzoinum S.zhejiangensisS.M.Hwang et L.L.Yu, fragrance Benzoinum S.odoratissimus Champ., China Benzoinum S.chinehsis Hu et S.Y.Liang, the southern regions of the Yunnan Province Benzoinum S.benzoinoides Graib, sumatra benzoin S.benzoin Dryand, Flos Lonicerae Benzoinum S.argentifolius H.L.Li, Herba Tephrosiae purpureae snowball S.calvescens Perk, the good leaf open country jasmine S.casearifolius Craib that grants, yellow fruit Benzoinum S.chrysocarpus H.L.Li, Sai Shanmei S.confusus Hemsl, hanging bead flower S.dasyanthus Perk, Styrax faberi Perk. S.faberi Perk, Flos Caryophylli snowball S.grandiflorus Griff, crow bell S.hemsleyanusDiels, Tibet snowball S.hookeri C.B.Clarke, the big seed snowball of snowball S.japonicus Sieb.et Zucc S.macrospermus C.Y.Wu, Folium paulowniae snowball S.mallotifolius C.Y.Wu, pink blossom snowball S.roseus Dunn, wrinkle leaf snowball S.rugosus Kurz, tingia snowball S.serrulatus Roxb, bolt leaf Benzoinum S.suberifolius Hook.et Arn, lobule Benzoinum S.wilsonii Rehd, S.ferrugineus, S.officinalis, any one fruit among the S.obassia Sieb.et Zucc etc., leaf, stem or tuber; Preferably, the fruit of Styrax plant.
Further, wherein said Benzoinum is a watt mountain Benzoinum.
Further again, wherein said Benzoinum is Benzoinum protogenic medicinal powder or extract.
Further, wherein said Benzoinum extract is the water of Styrax plant or the extract of organic solvent, and it is to contain Benzoinum 2-aryl benzofuran derivatives, and its percentage by weight is 40%～90%.
Further separation and Extraction is identified and is found to contain in this extract 2-aryl benzofuran derivatives monomer that one or more have following chemical constitution:
5-(3-hydroxyl) propyl group-7-methoxyl group-2-(3,4-dioxy methylene phenyl) benzofuran (being egonol)
5-(3-hydroxyl) propyl group-2-(3,4-dioxy methylene phenyl) benzofuran (being the de-methoxy egonol)
5-(3-hydroxyl) propyl group-7-hydroxyl-2-(3,4-dioxy methylene phenyl) benzofuran (being the demethyl egonol)
4 egonol acetass
5 de-methoxy egonol acetass
6 egonol butyrates
5-(3-oxypropylene group)-7-hydroxyl-2-(3, the 4-methylenedioxyphenyl) benzofuran
(trans)-5-(3-hydroxypropyl)-7-methoxyl group-2-(2,3-dihydro-3-hydroxymethyl-7-methoxyl group-2-(3-methoxyl group-4-hydroxy phenyl) benzofuranyl) benzofuran
9 egonols-glucoside
10 egonols-gentiobiose glycosides
11 egonols-gentianose glycosides
12 de-methoxies egonol-gentiobiose glycosides
(trans)-and 5-(3-hydroxypropyl)-2,3-dihydro-3-hydroxymethyl-2-(3-methoxyl group-4-hydroxy phenyl) benzofuran
Benzoinum extract is to be made by following method among the present invention:
A, the Styrax plant fruit pulverized after, water or alcohol, or aqueous alcohol is for extracting solvent extraction, extracting solution obtains total extractum through concentrating under reduced pressure;
B, above-mentioned total extractum loose with hot water is molten after, use petroleum ether extraction, to remove oiliness composition wherein;
After water layer after c, the extraction of b step adsorbs with macroporous resin column, first water eluting, reuse 30-95% ethanol elution pillar is collected ethanol elution, and is concentrated, dry, promptly gets the Styrax plant extract.
Wherein the described extraction solvent of a step is 50%～90% alcoholic solution, and the alcoholic solution consumption is 6-12 a times of medical material weight; The described eluant of c step is 95% ethanol.
The present invention also provides a kind of and has been used for the treatment of or the pharmaceutical composition of diseases such as prevention of arterial is atherosis, hyperlipemia, contains described Benzoinum protogenic medicinal powder or extract.
Further, this pharmaceutical composition is an active component with described Benzoinum protogenic medicinal powder or extract, add the medicament that acceptable accessories or complementary composition are prepared from, described preparation is tablet, capsule, soft capsule, oral liquid, granule, drop pill, injection.
1. tablet: comprise ordinary tablet, diaphragm, enteric coatel tablets etc.With above-mentioned Benzoinum protogenic medicinal powder or its extract dry powder; add that an amount of diluent such as starch, dextrin, manna are liquor-saturated, microcrystalline cellulose etc.; an amount of binding agent such as water, ethanol, starch slurry, gelatin, cellulose etc.; an amount of disintegrating agent such as dried starch, help methyl starch sodium, sodium alginate etc.; and proper amount of lubricating agent such as magnesium stearate, Pulvis Talci, Polyethylene Glycol etc.; wet granulation routinely, tabletting behind dry back granulate or the dry granulation.Wrap Film coated tablets in this way, may be configured as membrane material such as cellulose family, polyethylene glycols etc., coating divides in pack into airtight bottle or the aluminium-plastic panel routinely.
2. capsule: comprise conventional capsule agent, enteric coated capsule etc.Above-mentioned Benzoinum protogenic medicinal powder or its extract dry powder are added appropriate amount of auxiliary materials such as starch, calcium carbonate, mannitol, magnesium oxide, micropowder silica gel etc., moderate lubrication agent such as Pulvis Talci, magnesium stearate, glycol ester, silicone etc., and an amount of adhesive such as mineral oil, edible wet goods, be mixed into dry powder or make granule, be packed into gum cover, packing such as airtight aluminum-plastic packaged in.More than each dosage form can add an amount of sweeting agent, as D-xylose, xylitol, maltose alcohol, sweetleaf centautin, aspartame etc.
3. oral liquid: in the oral liquid preparation process, add medical additive with above-mentioned Benzoinum protogenic medicinal powder or its extract dry powder, as suspending agent (as sorbitol syrups, cellulose derivative, glucose/sucrose syrup, gelatin, stearic acid aluminium glue or hydrogenation edible fat); Emulsifying agent (for example lecithin, arabic gum or anhydrous sorbitol-oleate); Nonaqueous carrier (for example almond oil, oily ester, ethanol or refining vegetable oil); And antiseptic (for example methyl parahydroxybenzoate or propyl p-hydroxybenzoate or sorbic acid).As required, liquid preparation can also contain known buffer agent, correctives and fragrance ingredient, dyestuff and sweeting agent.
4. injection: with above-mentioned Benzoinum protogenic medicinal powder or its extract dry powder, add medicinal adjuvant, the reagent as suspending agent, stabilizing agent and/or dispersant and/or regulator solution osmotic pressure can be mixed with injection, preferred muscle, intravenous fluid.
Styrax plant of the present invention and extract all show inhibitory action to ACAT, especially with drug effect the best of watt mountain Benzoinum extract.And drug effect is clear and definite, and controllability provides a kind of new selection for clinical.
Above-mentioned Styrax plant protogenic medicinal powder or its extract can also be formed Chinese medicine compound or Chinese medicine and western medicine compound preparation jointly with other Chinese medicine and/or other chemicals according to foregoing of the present invention, and make multiple dosage forms such as oral tablet, capsule, oral liquid, injection according to conventional method, be used for prevention or diseases such as treatment atherosclerosis, hyperlipemia.
Obviously, according to foregoing of the present invention,,, can also make modification, replacement or the change of other various ways not breaking away under the above-mentioned basic fundamental thought of the present invention prerequisite according to the ordinary skill knowledge and the customary means of this area.
The specific embodiment
The specific embodiment of form is described in further detail foregoing of the present invention again by the following examples.But this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following example.All technology that realizes based on foregoing of the present invention all belong to scope of the present invention.
The preparation of 1 watt of mountain of embodiment Benzoinum protogenic medicinal powder
After getting the clean system of watt mountain Benzoinum dry fruit, pulverize according to a conventional method, sieve, making granularity is 60～80 purposes watt mountain Benzoinum fine powders, promptly gets a watt mountain Benzoinum protogenic medicinal powder.
The preparation of 2 watts of mountain Benzoinum extracts of embodiment
Watt mountain Benzoinum dry fruit 1000g adds 80% alcoholic solution 8L after the pulverizing, heating and refluxing extraction 1.5 hours, and filtering residue adds 80% alcoholic solution 6L again, and heating and refluxing extraction 1 hour is filtered.Merge filtrate twice, obtain total extractum 248g through concentrating under reduced pressure.After molten the loosing of total extractum usefulness 2L hot water, use the industrial petroleum ether extraction of 3L 5 times.Get D101 macroporous resin 2kg dress post, water layer with macroporous resin adsorption after, use the 15L water elution, eluent discards, use 95% ethanol elution pillar then, eluent gets extractum behind concentrating under reduced pressure, get dry powder 226g through vacuum or lyophilization again, adopts HPLC to analyze and measure its 2-aryl benzofuran content and is about 90% of gross weight.
The preparation of embodiment 3 high post spring Benzoinum extract
High post spring Benzoinum dry fruit 1000g adds 80% alcoholic solution 8L after the pulverizing, heating and refluxing extraction 1.5 hours, and filtering residue adds 80% alcoholic solution 6L again, and heating and refluxing extraction 1 hour is filtered.Merge filtrate twice, obtain total extractum 250g through concentrating under reduced pressure.After molten the loosing of total extractum usefulness 2L hot water, use the industrial petroleum ether extraction of 3L 5 times.Get D101 macroporous resin 2kg dress post, water layer with macroporous resin adsorption after, use the 15L water elution, eluent discards, use 95% ethanol elution pillar then, eluent gets extractum behind concentrating under reduced pressure, get dry powder 150g through vacuum or lyophilization again, and adopting HPLC to analyze and measure its 2-aryl benzofuran content is 82% of gross weight.
The preparation of embodiment 4 Chuxiong Benzoinum extracts
Chuxiong Benzoinum dry fruit 1000g adds 80% alcoholic solution 8L after the pulverizing, heating and refluxing extraction 1.5 hours, and filtering residue adds 80% alcoholic solution 6L again, and heating and refluxing extraction 1 hour is filtered.Merge filtrate twice, obtain total extractum 253g through concentrating under reduced pressure.After molten the loosing of total extractum usefulness 2L hot water, use the industrial petroleum ether extraction of 3L 5 times.Get D101 macroporous resin 2kg dress post, water layer with macroporous resin adsorption after, use the 15L water elution, eluent discards, and uses 95% ethanol elution pillar then, and eluent is gone up the 1.5kg polyamide column behind concentrating under reduced pressure, with 95% ethanol elution pillar, eluent gets extractum behind concentrating under reduced pressure, get dry powder 98g through vacuum or lyophilization again, adopts HPLC to analyze and measure its 2-aryl benzofuran content and is about 62% of gross weight.
The preparation of embodiment 5 the southern regions of the Yunnan Province Benzoinum extracts
The southern regions of the Yunnan Province Benzoinum dry fruit 1000g adds 80% alcoholic solution 8L after the pulverizing, heating and refluxing extraction 1.5 hours, and filtering residue adds 80% alcoholic solution 6L again, and heating and refluxing extraction 1 hour is filtered.Merge filtrate twice, obtain total extractum 253g through concentrating under reduced pressure.After molten the loosing of total extractum usefulness 2L hot water, use the industrial petroleum ether extraction of 3L 5 times.Get D101 macroporous resin 2kg dress post, water layer with macroporous resin adsorption after, use the 15L water elution, eluent discards, and uses 95% ethanol elution pillar then, and eluent is gone up the 1.5kg polyamide column behind concentrating under reduced pressure, with 95% ethanol elution pillar, eluent gets extractum behind concentrating under reduced pressure, get dry powder 98g through vacuum or lyophilization again, adopts HPLC to analyze and measure its 2-aryl benzofuran content and is about 40% of gross weight.
The preparation of 6 watts of mountain Benzoinum extracts of embodiment
Watt mountain Benzoinum dry fruit 1000g adds 90% alcoholic solution 12L after the pulverizing, heating and refluxing extraction 1.5 hours, and filtering residue adds 80% alcoholic solution 6L again, and heating and refluxing extraction 1 hour is filtered.Merge filtrate twice, obtain total extractum 248g through concentrating under reduced pressure.After molten the loosing of total extractum usefulness 2L hot water, use the industrial petroleum ether extraction of 3L 5 times.Get D101 macroporous resin 2kg dress post, water layer with macroporous resin adsorption after, use the 15L water elution, eluent discards, use 95% ethanol elution pillar then, eluent gets extractum behind concentrating under reduced pressure, get dry powder 230g through vacuum or lyophilization again, adopts HPLC to analyze and measure its 2-aryl benzofuran content and is about 86% of gross weight.
The preparation of embodiment 7 Chuxiong Benzoinum extracts
Chuxiong Benzoinum dry fruit 1000g adds 50% alcoholic solution 6L after the pulverizing, heating and refluxing extraction 1.5 hours, and filtering residue adds 80% alcoholic solution 6L again, and heating and refluxing extraction 1 hour is filtered.Merge filtrate twice, obtain total extractum 255g through concentrating under reduced pressure.After molten the loosing of total extractum usefulness 2L hot water, use the industrial petroleum ether extraction of 3L 5 times.Get D101 macroporous resin 2kg dress post, water layer with macroporous resin adsorption after, use the 15L water elution, eluent discards, and uses 30% ethanol elution pillar then, and eluent is gone up the 1.5kg polyamide column behind concentrating under reduced pressure, with 30% ethanol elution pillar, eluent gets extractum behind concentrating under reduced pressure, get dry powder 80g through vacuum or lyophilization again, adopts HPLC to analyze and measure its 2-aryl benzofuran content and is about 53% of gross weight.
The monomeric preparation of 8 watts of mountains of embodiment Benzoinum 2-aryl benzofuran derivatives
Watt benzoic fruit 2.2kg in mountain (dry weight) pulverizes the back with 80-90% industrial alcohol 25L lixiviate at room temperature 3 times, each 7 days.Lixiviating solution gets total extractum 550g behind vacuum concentration, it is suspended in the 5L hot water, respectively extracts 5 times with petroleum ether, chloroform and n-butyl alcohol successively, each 5L solvent, concentrated extract gets extractum respectively: petroleum ether part 16g, chloroform part 200g, n-butyl alcohol part 120g.The external activity screening is carried out in sampling, and chloroform and n-butyl alcohol part show that all having ACAT suppresses active.Chloroform is partly gone up silica gel column chromatography, use petroleum ether: acetone=10:1 successively, 5:1, the 0:1 eluting is divided into three sections Fr.1-3 with it.Fr.1 (30g) goes up silicagel column, and use petroleum ether: acetone=10:1 eluting obtains chemical compound 6 (60mg), 4 (30mg) and 5 (20mg).Fr.2 (150g) goes up silicagel column, and use petroleum ether: acetone=5:1 eluting obtains chemical compound 1 (95g), 2 (5g) and 7 (60mg).Fr.3 (15g) goes up silicagel column, uses CHCl
3: the MeOH=50:1 eluting obtains chemical compound 3 (45mg) and 8 (15mg).With getting 55g extractum after the desaccharide of D101 macroporous resin, last silica gel column chromatography is used CHCl to the n-butyl alcohol part successively earlier
3: MeOH=20:1,10:1,5:1, the 0:1 eluting obtains chemical compound 9 (4.2g), 10 (33g) and 11 (2.8g).
The preparation of embodiment 9 tablets
Tablet is formed: 2 watts of mountains of embodiment Benzoinum extract 0.5g
HPMC
LV100 30g
Lactose 70g
Magnesium stearate 1g (making 1000 altogether)
Watt mountain Benzoinum extract, HPMC, lactose, mixing is a binding agent system wet granular with 75% ethanol, cross 22 mesh sieves, 50 ℃ of dry 3h, 22 mesh sieve granulate add magnesium stearate mixing tabletting, every heavy 0.1g, be used for atherosclerosis or hyperlipidemia patient, oral, every day three times, each 1, be a course of treatment January.
The preparation of embodiment 10 capsules
Capsule is formed: high post spring Benzoinum extract 0.5g
Starch 100g
Magnesium stearate 1g (making 1000 altogether)
High post spring Benzoinum extract, starch, magnesium stearate, mixing, dress gum cover.Every dress 100mg is used for atherosclerosis or hyperlipidemia patient, and oral, every day three times, each 1, be a course of treatment January.
The preparation of embodiment 11 injection
Injection is formed: Chuxiong Benzoinum extract 0.5g
Tween 80 10mL
Sodium chloride 8g (making 1000ml altogether)
The Chuxiong Benzoinum extract adds 10%Na
2CO
3Transfer pH to 7.0-7.5, cold preservation filters, and adds tween 80, and NaCl adds the injection water to 1000mL, G
3Sintered filter funnel (glass) filters, packing, and embedding, 100 ℃ of circulation steam sterilization 30min are promptly.
The preparation of embodiment 12 compound tablet
Get the southern regions of the Yunnan Province Benzoinum extract 0.5g, soybean isoflavone 200g, tanshinone extract 200g, according to a conventional method, add corresponding adjuvant, make 1000 of tablet or capsules, every dress 200mg is used for atherosclerosis or hyperlipidemia patient, oral, every day three times, each 1, be a course of treatment January.
Below further specify beneficial effect of the present invention by the Styrax plant test of pesticide effectiveness.
Test example 1 Benzoinum extract is to the inhibition activity of ACAT
According to (the Identification of ACAT1-andACAT2-specific inhibitors using a novel of method like the mankind such as Rudel, cell-based fluorescence assay, Journal of Lipid Research, Volume 45,2004), use the fluorescopy method on a kind of cellular level to come the inhibition activity of authenticating compound to ACAT.
NBD-cholesterol is a kind of novel fluorogenic substrate, and NBD gives cholesterol does not but influence cholesterol with fluorescent characteristic absorption and internal metabolism function.NBD-cholesterol also has a kind of very important characteristic: the fluorescence intensity of NBD-cholesterol depends on its residing environment, NBD-cholesterol sends fluorescence hardly or sends extremely weak fluorescence when being in a kind of polar environment, and NBD-cholesterol just can send very strong fluorescence when being in a kind of nonpolar environment.NBD-cholesterol itself is a kind of polar molecule, but enter in the cell when it is absorbed, under the catalysis of ACAT, generate corresponding cholesteryl ester, just become nonpolar molecule by a kind of polar molecule, and be gathered into the fat granule, form a kind of nonpolar environment.This just provides a kind of ACAT of detection active very easy method.Cholesterol is synthetic mainly to carry out in liver with metabolism.This experimental selection HepG
2Screen cell as supplying, and detected HepG by methods such as RT-PCR
2The expression of cell ACAT.
ACAT suppresses the concrete scheme of determination of activity: inoculation HepG
2Cell is in 96 orifice plates, 20,000/hole, 37 ℃ of overnight incubation, culture medium is abandoned in suction, every hole adds the fresh low sugar DMEM culture medium of 160 μ L earlier, the aerial 20 μ L PBS that add of blank and negative control, (each sample is done 10 holes, and testing sample starter hole concentration is 300 μ g/ml for Benzoinum extract sample that added respectively by prospect hole to prepare in advance and positive control medicine SANDOZ58-035 (Sigma company provides) 20 μ L, positive control sample starter hole concentration is 30 μ g/ml, dilute successively by 3 times of dilution factors respectively, make 10 Concentraton gradient), cultivated again 1 hour for 37 ℃, blank group adds 20 μ L PBS, all the other each holes add the substrate NBD-cholesterol 20 μ L that prepare in advance, and final concentration is 2 μ g/ml, 37 ℃ of overnight incubation, PBS washes 3 times, uses WALLAC Victor
2Measure fluorescent value, excitation wavelength is 485nm, and emission wavelength is 535nm, calculates suppression ratio, suppression ratio=(feminine gender-sample)/(feminine gender-blank) * 100% according to fluorescent value.According to suppression ratio, the 4Parameter Logistic Model that uses in the Xlfit software calculates IC
50Value.The result is as shown in table 1:
Table 1 Benzoinum protogenic medicinal powder and extract thereof are to the inhibitory action of ACAT
| Medicine | IC 50(μg/mL) |
| Embodiment 1 protogenic medicinal powder | 68.11 |
| Embodiment 2 extracts | 25.14 |
| Embodiment 3 extracts | 32.59 |
| Embodiment 4 extracts | 41.26 |
| Embodiment 5 extracts | 56.77 |
| SANDOZ58-035 | 8.72 |
As can be seen from Table 1, primary medicine of the embodiment of the invention 1～5 Benzoinum and extract thereof all show inhibitory action to ACAT.The IC of 2 watts of mountain Benzoinum extracts of embodiment wherein
50Be worth minimumly, show that its effect is best.Above result shows that Styrax plant extract of the present invention has the ACAT inhibitory action, can be used as a kind of new selection of preparation ACAT inhibitor medicaments.
Claims (13)
1, Styrax plant and extract thereof are preparing acyl-CoA: the application in the chole-sterol acyltransferase inhibitor class medicine.
2, purposes according to claim 1 is characterized in that: described medicine be the treatment or prevention of arterial is atherosis, the medicine of hyperlipemia.
3, purposes according to claim 1 is characterized in that: described medicine is that treatment or prevention angina pectoris, myocardial infarction, cerebral infarction, Alzheimer, acute coronary syndrome, PTCA or support are placed the medicine of back coronary restenosis.
4, purposes according to claim 1 is characterized in that: described medicine is the medicine that is used to regulate the sebaceous gland function, suppresses the excessive generation of sebum.
5, according to each described purposes of claim 1～4, it is characterized in that: described Styrax plant derives from a watt mountain Benzoinum Styrax perkinsiae, high post spring Benzoinum S.macranthus Perk., Chuxiong Benzoinum S.limprichtii Lingelsh et Borza, Styrax tonkinensis S.tonkinensis (Pierre) Craib et Hartw., Zhejiang Benzoinum S.zhejiangensis S.M.Hwang et L.L.Yu, fragrance Benzoinum S.odoratissimus Champ., China Benzoinum S.chinehsis Hu et S.Y.Liang, the southern regions of the Yunnan Province Benzoinum S.benzoinoides Graib, sumatra benzoin S.benzoin Dryand, Flos Lonicerae Benzoinum S.argentifolius H.L.Li, Herba Tephrosiae purpureae snowball S.calvescens Perk, good gift leaf snowball S.casearifolius Craib, yellow fruit Benzoinum S.chrysocarpus H.L.Li, Sai Shanmei S.confususHemsl, hanging bead flower S.dasyanthus Perk, Styrax faberi Perk. S.faberi Perk, Flos Caryophylli snowball S.grandiflorus Griff, crow bell S.hemsleyanus Diels, Tibet snowball S.hookeri C.B.Clarke, snowball S.japonicus Sieb.et Zucc, big seed snowball S.macrospermus C.Y.Wu, Folium paulowniae snowball S.mallotifolius C.Y.Wu, pink blossom snowball S.roseus Dunn, wrinkle leaf snowball S.rugosus Kurz, tingia snowball S.serrulatus Roxb, bolt leaf Benzoinum S.suberifolius Hook.et Am, lobule Benzoinum S.wilsonii Rehd, S.ferrugineus, S.officinalis, any one fruit among the S.obassia Sieb.et Zucc, leaf, stem or tuber.
6, purposes according to claim 5 is characterized in that: described Benzoinum is a watt mountain Benzoinum.
7, according to the described purposes of one of claim 1～6, it is characterized in that: described Benzoinum is Benzoinum protogenic medicinal powder or extract.
8, purposes according to claim 7 is characterized in that: described Benzoinum extract is the extract of water or organic solvent.
9, according to claim 7 or 8 described purposes, it is characterized in that: contain Benzoinum 2-aryl benzofuran derivatives in the described Benzoinum extract, its percentage by weight is 40%～90%.
10, according to Claim 8 or 9 described purposes, it is characterized in that: described Benzoinum extract is to be made by following method:
A, the Styrax plant fruit pulverized after, water or ethanol, or aquiferous ethanol is for extracting solvent extraction, extracting solution obtains total extractum through concentrating under reduced pressure;
B, above-mentioned total extractum loose with hot water is molten after, use petroleum ether extraction, to remove oiliness composition wherein;
After water layer after c, the extraction of b step adsorbs with macroporous resin column, first water eluting, reuse 30-95% ethanol elution pillar is collected ethanol elution, and is concentrated, dry, promptly gets the Styrax plant extract.
11, purposes according to claim 10 is characterized in that: the described extraction solvent of a step is 50%～90% alcoholic solution in the described preparation method, and the alcoholic solution consumption is 6-12 a times of medical material weight; The described eluant of c step is 95% ethanol.
12, a kind of be used for the treatment of or prevention of arterial is atherosis, the pharmaceutical composition of hyperlipemia, it is characterized in that with each described Benzoinum protogenic medicinal powder of claim 7～11 or extract be active component, add the medicament that acceptable accessories or complementary composition are prepared from.
13, pharmaceutical composition according to claim 12 is characterized in that described preparation is tablet, capsule, soft capsule, oral liquid, granule, drop pill or injection.
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| CN2009100056311A CN101502541B (en) | 2008-02-04 | 2009-01-20 | Styrax plant and use of extract thereof |
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| CN200810045359.5 | 2008-02-04 | ||
| CN200810045359 | 2008-02-04 | ||
| CN2009100056311A CN101502541B (en) | 2008-02-04 | 2009-01-20 | Styrax plant and use of extract thereof |
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| CN101502541B CN101502541B (en) | 2011-12-28 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107080023A (en) * | 2017-06-07 | 2017-08-22 | 郴州五盖山天时生态农业科技开发有限公司 | A kind of snowball tea and preparation method thereof |
| CN110668946A (en) * | 2019-10-28 | 2020-01-10 | 广东药科大学 | Compound Stybenpropol A and application thereof in preventing and treating atherosclerosis |
| CN110742833A (en) * | 2019-11-28 | 2020-02-04 | 广州环亚化妆品科技有限公司 | Acne-removing, whitening and anti-aging essential oil composition as well as preparation method and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US6133326A (en) * | 1994-08-31 | 2000-10-17 | Pfizer Inc | Compositions and methods for decreasing sebum production |
| JP2007508291A (en) * | 2003-10-09 | 2007-04-05 | ワーナー−ランバート カンパニー リミテッド ライアビリティー カンパニー | Pharmaceutical composition comprising a malonamide derivative for reducing sebum production |
| CN1313108C (en) * | 2005-09-02 | 2007-05-02 | 于勇春 | Medicine for treating cardiovascular and cerebrovascular disease |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107080023A (en) * | 2017-06-07 | 2017-08-22 | 郴州五盖山天时生态农业科技开发有限公司 | A kind of snowball tea and preparation method thereof |
| CN107080023B (en) * | 2017-06-07 | 2021-04-30 | 郴州五盖山天时生态农业科技开发有限公司 | Wild jasmine tea and preparation method thereof |
| CN110668946A (en) * | 2019-10-28 | 2020-01-10 | 广东药科大学 | Compound Stybenpropol A and application thereof in preventing and treating atherosclerosis |
| CN110668946B (en) * | 2019-10-28 | 2021-11-26 | 广东药科大学 | Compound Stybenpropol A and application thereof in preventing and treating atherosclerosis |
| CN110742833A (en) * | 2019-11-28 | 2020-02-04 | 广州环亚化妆品科技有限公司 | Acne-removing, whitening and anti-aging essential oil composition as well as preparation method and application thereof |
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| CN101502541B (en) | 2011-12-28 |
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